An international multicentre clinical trial comparing two chemotherapy regimens in patients with advanced anal cancer

An International Multicentre Open Label Randomised Phase II Advanced Anal Cancer Trial Comparing Cisplatin plus 5-fluorouracil versus Carboplatin plus Weekly Paclitaxel in Patients with Inoperable Locally Recurrent or Metastatic Disease - InterAACT A Multicentre Randomised Phase II Advanced Anal Cancer Trial

Status

Not yet recruiting

Phases

Unknown

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2013-001949-13-GB

Enrollment

Registered

2013-09-20

Start date

2013-10-31

Completion date

Unknown

Last updated

2015-08-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Inoperable, locally recurrent or metastatic squamous cell carcinoma of the anus MedDRA version: 18.0 Level: LLT Classification code 10041815 Term: Sq cell Ca anus System Organ Class: 100000004864

Interventions

Trade Name: Cisplatin Product Name: Cisplatin Pharmaceutical Form: Solution for infusion INN or Proposed INN: cisplatin CAS Number: 15663-27-1 Concentration unit: mg/ml milligram(s)/millilitre Concent

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Histologically or cytologically verified, uni-dimensionally measurable, inoperable, locally recurrent or metastatic squamous cell carcinoma of the anus. 2. Age =18 years. 3. ECOG PS =2. 4. Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1. 5. Previous definitive chemo-radiation is permitted for early stage squamous cell carcinoma of the anus. 6. HIV+ patients will be considered eligible with a CD4 count of =200. 7. Adequate cardiac and respiratory function; absolute neutrophil count (ANC) =1.5x109/l; white blood cell (WBC) count =3x109/l; platelets =100x109/l; haemoglobin (Hb) =9g/dl; creatinine clearance =50ml/minute; serum bilirubin =1.5x upper limit of normal (ULN); alanine transaminase (ALT)/aspartate transaminase (AST) =2.5x ULN; alkaline phosphatase (ALP) =3x ULN. 8. Life expectancy of at least 3 months. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20

Exclusion criteria

Exclusion criteria: 1. Tumours of adenocarcinoma, melanoma, small cell and basal cell histology are excluded. 2. Previous chemotherapy, radiotherapy or other investigational drug for surgically unresectable locally recurrent or advanced squamous cell carcinoma of the anus. 3. Current or recent (within 30 days of first study dosing) treatment with another investigational drug or participation in another investigational study. 4. Documented or symptomatic brain metastases and/or central nervous system metastases or leptomeningeal disease. 5. Surgery or palliative radiotherapy within 28 days of randomisation. 6. Clinically significant (i.e. active) cardiac disease (e.g. symptomatic coronary artery disease, uncontrolled cardiac arrhythmia, or myocardial infarction within the last 6 months). Any history of clinically significant cardiac failure. 7. History of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan. 8. Lack of physical integrity of the gastro-intestinal tract, malabsorption syndrome (naso-gastric or jejunostomy feeding tube is permitted). 9. Acute hepatitis C and/or chronic active hepatitis B infection. 10. Serious active infection requiring i.v. antibiotics at enrolment. 11. Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer. 12. Other clinically significant disease or co-morbidity that may adversely affect the safe delivery of treatment within this trial. 13. Known hypersensitivity to any of the study drugs or excipients. 14. Pregnant or lactating females.

Design outcomes

Primary

Measure	Time frame
Main Objective: The primary objective of the study is to compare the activity, in terms of overall response rate, of two combination chemotherapy regimens (cisplatin plus 5-fluorouracil vs. carboplatin plus weekly paclitaxel) for the first line treatment of patients with inoperable relapsed or metastatic squamous cell carcinoma of the anus. The results of the study will be used to inform the design of future phase III trials testing the addition of a targeted agent to the preferred chemotherapy regimen. ;Secondary Objective: The secondary objectives of the study are to provide estimates of differences in survival, toxicity and quality-of-life (QoL) endpoints between the two study arms. Exploratory biomarker research will also be undertaken in order to further investigate the role of the epidermal growth factor receptor (EGFR) pathway and other molecular pathways in predicting response or resistance to systemic chemotherapy. ;Primary end point(s): The primary endpoint of thes study is best overall response rate. ;Timepoint(s) of evaluation of this end point: Best overall response rate is defined as the percentage of patients achieving confirmed partial(PR) or complete responses (CR) as per RECIST v1.1 by 24 weeks post treatment start in the intention to treat population. The ORR will be summarised as the percentage (including 95% confidence intervals) of responders and will be compared between groups using Mantel-Haenszel chi-squared test stratifying by country.	—

Measure

Time frame

Main Objective: The primary objective of the study is to compare the activity, in terms of overall response rate, of two combination chemotherapy regimens (cisplatin plus 5-fluorouracil vs. carboplatin plus weekly paclitaxel) for the first line treatment of patients with inoperable relapsed or metastatic squamous cell carcinoma of the anus. The results of the study will be used to inform the design of future phase III trials testing the addition of a targeted agent to the preferred chemotherapy regimen. ;Secondary Objective: The secondary objectives of the study are to provide estimates of differences in survival, toxicity and quality-of-life (QoL) endpoints between the two study arms. Exploratory biomarker research will also be undertaken in order to further investigate the role of the epidermal growth factor receptor (EGFR) pathway and other molecular pathways in predicting response or resistance to systemic chemotherapy. ;Primary end point(s): The primary endpoint of thes study is best overall response rate. ;Timepoint(s) of evaluation of this end point: Best overall response rate is defined as the percentage of patients achieving confirmed partial(PR) or complete responses (CR) as per RECIST v1.1 by 24 weeks post treatment start in the intention to treat population. The ORR will be summarised as the percentage (including 95% confidence intervals) of responders and will be compared between groups using Mantel-Haenszel chi-squared test stratifying by country.

—

Secondary

Measure	Time frame
Secondary end point(s): - To assess the feasibility of conducting this study globally in 50 international centres and recruiting within a reasonable time frame. This will be measured by (i) the proportion of centres that successfully engage in the study, non-engagement being measured by the proportion of centres leaving the study or recruiting very few patients (<2) with reasons related to rarity of the disease/ toxicity of regimens/ any other logistical issues and (ii) overall recruitment rate. We anticipate and would be able to confirm feasibility if 80% of the centres fully engaged with the study. The aim would be to recruit 80 patients in 36 months (10 by month 6, 20 by month 12, 50 by month 24 and 80 by month 36) These centres would open at an average rate of 2/month for six months, starting with UK centres expected to recruit approximately 10 patients per year and then the international centres expected to recruit approximately 10 patients per year. After 36 months we expect to have recruited 80 patients. - PFS. This is calculated from the date of randomisation to the date of confirmed clinical/radiological progression or death from any cause. Patients who are lost to follow-up, withdraw from follow-up or alive and progression free will be censored at the date of last follow-up. - OS. This is calculated from the date of randomisation to the date of death from any cause. Patients, in whom no death is recorded, will be censored at the date they were last seen alive. - DCR at 12 and 24 weeks post treatment start. This is defined as CR, PR or SD, and will be assessed in accordance with the RECIST criteria v1.1. - Best ORR of non-irradiated lesions. This is defined as the percentage of patients achieving confirmed PR or CR as per RECIST v1.1 of non-irradiated sites of disease by 24 weeks post treatment start in the ITT population. - Anti-tumour activity and magnitude of response as captured by waterfall plot analyses. - Toxicity. Toxicity will be graded accordi	—

Measure

Time frame

Secondary end point(s): - To assess the feasibility of conducting this study globally in 50 international centres and recruiting within a reasonable time frame. This will be measured by (i) the proportion of centres that successfully engage in the study, non-engagement being measured by the proportion of centres leaving the study or recruiting very few patients (<2) with reasons related to rarity of the disease/ toxicity of regimens/ any other logistical issues and (ii) overall recruitment rate. We anticipate and would be able to confirm feasibility if 80% of the centres fully engaged with the study. The aim would be to recruit 80 patients in 36 months (10 by month 6, 20 by month 12, 50 by month 24 and 80 by month 36) These centres would open at an average rate of 2/month for six months, starting with UK centres expected to recruit approximately 10 patients per year and then the international centres expected to recruit approximately 10 patients per year. After 36 months we expect to have recruited 80 patients. - PFS. This is calculated from the date of randomisation to the date of confirmed clinical/radiological progression or death from any cause. Patients who are lost to follow-up, withdraw from follow-up or alive and progression free will be censored at the date of last follow-up. - OS. This is calculated from the date of randomisation to the date of death from any cause. Patients, in whom no death is recorded, will be censored at the date they were last seen alive. - DCR at 12 and 24 weeks post treatment start. This is defined as CR, PR or SD, and will be assessed in accordance with the RECIST criteria v1.1. - Best ORR of non-irradiated lesions. This is defined as the percentage of patients achieving confirmed PR or CR as per RECIST v1.1 of non-irradiated sites of disease by 24 weeks post treatment start in the ITT population. - Anti-tumour activity and magnitude of response as captured by waterfall plot analyses. - Toxicity. Toxicity will be graded accordi

—

Countries

Australia, Brazil, European Union, Norway, United Kingdom, United States

Contacts

Public ContactAnnette Bryant

Royal Marsden NHS Foundation Trust

annette.bryant@rmh.nhs.uk02086613637

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026